講演情報
[O4-6]大腸癌患者でのASNS-mRNAの予後予測マーカーとしての意義
*志村 匡信1、北嶋 貴仁1,2、小池 勇樹1、東 浩輝1、天白 成1、嶌村 麻生1、高木 里英子1、横山 歩乃加1、山本 晃1、市川 崇1,3、浦谷 亮1、今岡 裕基1、川村 幹雄1、安田 裕美1、大北 喜基1、吉山 繁幸1、小林 美奈子1,3、大井 正貴1、奥川 喜永1,2、問山 裕二1 (1. 三重大学大学院消化管小児外科学、2. 三重大学病院ゲノム診療科、3. 三重大学大学院臨床外科感染制御学講座)
Background Asparagine synthetase (ASNS) catalyzes the synthesis of asparagine from aspartate and glutamine, which enables cancer cells to adapt to environmental stress. While there are plural evidence that ASNS possess cancer progressive role in several solid malignancies, the oncogenic importance of ASNS has not fully elucidated in colorectal cancer (CRC) patients.
Methods In this study, we evaluated the expression of ASNS-mRNA in tumor tissue of Stage1–4 CRC patients (n=292) and adjacent normal mucosa (n=39) by quantitative real-time polymerase chain reaction (qRT-PCR). We evaluated the association between ASNS-mRNA expression and clinico-patological characters, and we evaluated the prognostic biomarker potential of ASNS-mRNA expression. Patients were dichotomized into high and low ASNS groups by using Youden index for overall survival (OS) or recurrence free survival (RFS).
Results ASNS-mRNA expression was significantly higher in CRC tissue than in adjacent normal mucosa (p=0.003). There was no correlation between ASNS-mRNA expression and clinico-pathological factors. While kaplan meier analysis for OS did not significantly stratify patients’ prognosis between high/low expression group (p=0.14), RFS analysis revealed that patients with high-ASNS showed significantly poorer RFS than those with low-ASNS (p=0.027). Moreover, cox-proportional multivariate analysis for RFS demonstrated that ASNS high expression was identified as an independent risk factor for poorer RFS with a corresponding hazard ratio of 1.87 (p=0.03).
Conclusion We suggest that ASNS might be an important recurrence-predictive biomarker in CRC patients.
Methods In this study, we evaluated the expression of ASNS-mRNA in tumor tissue of Stage1–4 CRC patients (n=292) and adjacent normal mucosa (n=39) by quantitative real-time polymerase chain reaction (qRT-PCR). We evaluated the association between ASNS-mRNA expression and clinico-patological characters, and we evaluated the prognostic biomarker potential of ASNS-mRNA expression. Patients were dichotomized into high and low ASNS groups by using Youden index for overall survival (OS) or recurrence free survival (RFS).
Results ASNS-mRNA expression was significantly higher in CRC tissue than in adjacent normal mucosa (p=0.003). There was no correlation between ASNS-mRNA expression and clinico-pathological factors. While kaplan meier analysis for OS did not significantly stratify patients’ prognosis between high/low expression group (p=0.14), RFS analysis revealed that patients with high-ASNS showed significantly poorer RFS than those with low-ASNS (p=0.027). Moreover, cox-proportional multivariate analysis for RFS demonstrated that ASNS high expression was identified as an independent risk factor for poorer RFS with a corresponding hazard ratio of 1.87 (p=0.03).
Conclusion We suggest that ASNS might be an important recurrence-predictive biomarker in CRC patients.